Candidiasis, Invasive
Conditions
Brief summary
The study will evaluate the safety, tolerability, and efficacy of caspofungin as compared with amphotericin B deoxycholate in the treatment of invasive candidiasis in neonates and infants. The primary hypothesis to be tested in the study is that caspofungin will be superior to amphotericin B deoxycholate with regard to the proportion of participants with fungal-free survival at the 2-week post-therapy follow-up visit.
Interventions
DRUGCaspofungin
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Months
Healthy volunteers
No
Inclusion criteria
* Culture-confirmed invasive Candida infection
Exclusion criteria
* Candida disease limited to the oropharynx, esophagus, or other mucosal or superficial skin surfaces * Positive culture for Candida only from sputum, broncho-alveolar lavage, catheter tip, or previously placed indwelling non-vascular catheters or drains * Prosthetic device as the suspected site of Candida infection * Active co-infection with a non-Candida fungal organism * Received \>48 hours of systemic antifungal treatment since the positive Candida index culture was collected as therapy for the present episode of invasive candidiasis * Failed prior systemic antifungal therapy for the present episode of invasive candidiasis * Diagnosis of acute hepatitis or cirrhosis * Scheduled or anticipated to receive rifampin or other systemic antifungal therapy while on study therapy * History (including participant's mother) of allergy, hypersensitivity, or any serious reaction to caspofungin or other member of the echinocandin class, or to amphotericin B deoxycholate or other member of the polyene class * Severe congenital disorder known to lower immune response
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Fungal-free Survival Through the 2-week Post-therapy Period | Up to 104 days | Fungal-free survival is those participants who survived up to 2 weeks post-therapy, and had documented microbiological eradication of Candida species (sp.) from follow-up cultures collected after the initiation of study therapy. Microbiological eradication denotes negative follow-up cultures for Candida sp. from the site of infection. If a culture is not obtained on the day of assessment, the last culture after study entry may be used to assist in the assessment of microbiological eradication. If the last culture is negative for Candida sp., then microbiological eradication would be considered achieved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Fungal-free Survival Through the End of Study Treatment | Up to 90 days | Fungal-free survival is those participants who survived up to end of study treatment, and had documented microbiological eradication of Candida sp. from follow-up cultures collected after the initiation of study therapy. Microbiological eradication denotes negative follow-up cultures for Candida sp. from the site of infection. If a culture is not obtained on the day of assessment, the last culture after study entry may be used to assist in the assessment of microbiological eradication. If the last culture is negative for Candida sp., then microbiological eradication would be considered achieved. |
| Number of Participants With an Adverse Event (AE) | 8 weeks after end of study therapy (up to 146 days) | An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE. |
Participant flow
Recruitment details
Participants less than 3 months of age with invasive candidiasis were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Caspofungin Caspofungin 2 mg/kg intravenous once daily for ≥14 days after documented negative culture and improvement of clinical signs and symptoms, for a maximum of 90 days treatment | 34 |
| Amphotericin B Deoxycholate Amphotericin B deoxycholate 1 mg/kg intravenous once daily for ≥14 days after documented negative culture and improvement of clinical signs and symptoms, for a maximum of 90 days treatment | 17 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 3 | 3 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Technical Problems | 1 | 0 |
Baseline characteristics
| Characteristic | Caspofungin | Total | Amphotericin B Deoxycholate |
|---|---|---|---|
| Age, Continuous | 31.1 Days STANDARD_DEVIATION 20.9 | 31.7 Days STANDARD_DEVIATION 21.5 | 32.8 Days STANDARD_DEVIATION 23.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 19 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 28 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 19 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 21 Participants | 8 Participants |
| Sex: Female, Male Female | 14 Participants | 24 Participants | 10 Participants |
| Sex: Female, Male Male | 20 Participants | 27 Participants | 7 Participants |
| Weight | 1982.1 Grams STANDARD_DEVIATION 980.6 | 2042.9 Grams STANDARD_DEVIATION 1175.5 | 2160.9 Grams STANDARD_DEVIATION 1513.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 33 | 3 / 16 |
| other Total, other adverse events | 23 / 33 | 15 / 16 |
| serious Total, serious adverse events | 7 / 33 | 9 / 16 |
Outcome results
Primary
Percentage of Participants With Fungal-free Survival Through the 2-week Post-therapy Period
Fungal-free survival is those participants who survived up to 2 weeks post-therapy, and had documented microbiological eradication of Candida species (sp.) from follow-up cultures collected after the initiation of study therapy. Microbiological eradication denotes negative follow-up cultures for Candida sp. from the site of infection. If a culture is not obtained on the day of assessment, the last culture after study entry may be used to assist in the assessment of microbiological eradication. If the last culture is negative for Candida sp., then microbiological eradication would be considered achieved.
Time frame: Up to 104 days
Population: Participants who received at least 1 full dose of study therapy and had a documented (culture-confirmed) diagnosis of invasive candidiasis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caspofungin | Percentage of Participants With Fungal-free Survival Through the 2-week Post-therapy Period | 71.0 Percentage of Participants |
| Amphotericin B Deoxycholate | Percentage of Participants With Fungal-free Survival Through the 2-week Post-therapy Period | 68.8 Percentage of Participants |
95% CI: [-24.3, 27.7]
Secondary
Number of Participants With an Adverse Event (AE)
An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Time frame: 8 weeks after end of study therapy (up to 146 days)
Population: All participants as treated
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caspofungin | Number of Participants With an Adverse Event (AE) | 28 Participants |
| Amphotericin B Deoxycholate | Number of Participants With an Adverse Event (AE) | 16 Participants |
Secondary
Percentage of Participants With Fungal-free Survival Through the End of Study Treatment
Fungal-free survival is those participants who survived up to end of study treatment, and had documented microbiological eradication of Candida sp. from follow-up cultures collected after the initiation of study therapy. Microbiological eradication denotes negative follow-up cultures for Candida sp. from the site of infection. If a culture is not obtained on the day of assessment, the last culture after study entry may be used to assist in the assessment of microbiological eradication. If the last culture is negative for Candida sp., then microbiological eradication would be considered achieved.
Time frame: Up to 90 days
Population: Participants who received at least 1 full dose of study therapy and had a documented (culture-confirmed) diagnosis of invasive candidiasis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caspofungin | Percentage of Participants With Fungal-free Survival Through the End of Study Treatment | 71.0 Percentage of Participants |
| Amphotericin B Deoxycholate | Percentage of Participants With Fungal-free Survival Through the End of Study Treatment | 75.0 Percentage of Participants |
95% CI: [-30.2, 22.6]